Wang Cai-hua, Gao Zhi-qiang, Ye Bing, Xie Chuan-gao, Qian Ke-da, Cai Jian-ting, Du Qin
Department of Gastroenterology, Second Affiliated Hosipital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Zhonghua Yi Xue Za Zhi. 2006 Sep 26;86(36):2552-5.
To study the effect of emodin on pancreatic fibrosis and potential mechanism thereof.
Fifty SD rats were randomly divided into 5 equal groups: normal control group, model control group, low-dose emodin-treated group, mediate-dose emodin-treated group, and high-dose emodin-treated group. The rats of the latter 4 groups underwent infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct so as to establish models of pancreatic fibrosis. The emodin-treated rats were fed with different doses of emodin (20, 40, and 80 mg/kg body weight), while the normal and model control groups received 0.9% sodium chloride solution instead. Twenty-eight days later the rats were killed, blood samples were collected, and their pancreases were taken out. The serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. The histopathological alterations were studied by optical microscopy. The expression of collagen was examined by Van Gieson staining. Western blotting was used to detect the protein expression of transforming growth factor-beta(1) (TGF-beta(1)).
(1) The serum level of HA of the low-dose, mediate-dose, and high-dose emodin-treated groups were 87 microg/L +/- 22 microg/L, 78 microg/L +/- 25 microg/L, and 62 microg/L +/- 19 microg/L respectively, all significantly lower than that of the model control group (113 microg/L +/- 27 microg/L, P < 0.05 or < 0.01). The serum levels of laminin in the low-dose, mediate-dose, and high-dose emodin-treated groups were 67 microg/L +/- 14 microg/L, 57 microg/L +/- 12 microg/L, and 44 microg/L +/- 10 microg/L respectively, all significantly lower than that of the model control group (86 microg/L +/- 17 microg/L, P < 0.05 or P < 0.01); (2) The degrees of fibrosis of the emodin-treated groups were obviously ameliorated in comparison with the model control group, the higher the dose of emodin the more improved the pathological changes, especially in the high-dose emodin-treated group (P < 0.05). (3) The percentages of collagen positive cells of the low-dose, mediate-dose, and high-dose emodin-treated groups were 39% +/- 7%, 38% +/- 4%, and 36% +/- 5% respectively, all lower than that of the model control group (42% +/- 6%), with a significant difference between the high-dose emodin-treated group and the model control group (P < 0.05). (4) The protein content of TGF-beta(1) of the low-dose, mediate-dose, and high-dose emodin-treated groups were 44.3% +/- 2.1%, 39.2% +/- 1.8%, and 28.8% +/- 1.6% respectively, all significantly lower than that of the model control group (60.7% +/- 1.7%, all P < 0.05), and the protein content of TGF-beta(1) of the high-dose emodin-treated group was significantly lower than those of the other 2 emodin-treated groups (both P < 0.05).
Emoidn has an anti-fibrosis effect on pancreatic fibrosis, which maybe related to the content of TGF-beta(1) protein.
研究大黄素对胰腺纤维化的作用及其潜在机制。
将50只SD大鼠随机分为5组,每组10只:正常对照组、模型对照组、大黄素低剂量治疗组、大黄素中剂量治疗组和大黄素高剂量治疗组。后4组大鼠经胰胆管注入三硝基苯磺酸(TNBS)以建立胰腺纤维化模型。给予大黄素治疗组大鼠不同剂量的大黄素(20、40和80mg/kg体重),正常对照组和模型对照组大鼠给予0.9%氯化钠溶液。28天后处死大鼠,采集血样,并取出胰腺。采用放射免疫法测定血清透明质酸(HA)和层粘连蛋白(LN)水平。通过光学显微镜观察组织病理学改变。采用Van Gieson染色检测胶原蛋白的表达。采用蛋白质印迹法检测转化生长因子-β1(TGF-β1)的蛋白表达。
(1)大黄素低剂量、中剂量和高剂量治疗组血清HA水平分别为87μg/L±22μg/L、78μg/L±25μg/L和62μg/L±19μg/L,均显著低于模型对照组(113μg/L±27μg/L,P<0.05或<0.01)。大黄素低剂量、中剂量和高剂量治疗组血清层粘连蛋白水平分别为67μg/L±14μg/L、57μg/L±12μg/L和44μg/L±10μg/L,均显著低于模型对照组(86μg/L±17μg/L,P<0.05或P<0.01);(2)与模型对照组相比,大黄素治疗组的纤维化程度明显改善,大黄素剂量越高,病理变化改善越明显,尤其是大黄素高剂量治疗组(P<0.05)。(3)大黄素低剂量、中剂量和高剂量治疗组胶原蛋白阳性细胞百分比分别为39%±7%、38%±4%和36%±5%,均低于模型对照组(42%±6%),大黄素高剂量治疗组与模型对照组之间差异有统计学意义(P<0.05)。(4)大黄素低剂量、中剂量和高剂量治疗组TGF-β1蛋白含量分别为44.3%±2.1%、39.2%±1.8%和28.8%±1.6%,均显著低于模型对照组(60.7%±1.7%,均P<0.05),大黄素高剂量治疗组TGF-β1蛋白含量显著低于其他2个大黄素治疗组(均P<0.05)。
大黄素对胰腺纤维化具有抗纤维化作用,其机制可能与TGF-β1蛋白含量有关。